ProHance

WARNINGS

Nephrogenic Systemic Fibrosis (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk
for nephrogenic systemic fibrosis (NSF) among patients with impaired
elimination of the drugs. Avoid use of GBCAs among these patients unless the
diagnostic information is essential and not available with non-contrast enhanced
MRI or other modalities. The GBCA-associated NSF risk appears highest for
patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m²) as well
as patients with acute kidney injury. The risk appears lower for patients with
chronic, moderate kidney disease (GFR 30-59 mL/min/1.73m²) and little, if any,
for patients with chronic, mild kidney disease (GFR 60-89 mL/min/1.73m²). NSF
may result in fatal or debilitating fibrosis affecting the skin, muscle and
internal organs. Report any diagnosis of NSF following ProHance administration
to Bracco Diagnostics (1-800-257-5181) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch). Screen patients
for acute kidney injury and other conditions that may reduce renal function.
Features of acute kidney injury consist of rapid (over hours to days) and
usually reversible decrease in kidney function, commonly in the setting of
surgery, severe infection, injury or drug-induced kidney toxicity. Serum
creatinine levels and estimated GFR may not reliably assess renal function in
the setting of acute kidney injury. For patients at risk for chronically reduced
renal function (e.g., age > 60 years, diabetes mellitus or chronic hypertension),
estimate the GFR through laboratory testing.

Among the factors that may increase the risk for NSF are
repeated or higher than recommended doses of a GBCA and the degree of renal
impairment at the time of exposure. Record the specific GBCA and the dose
administered to a patient. For patients at highest risk for NSF, do not exceed
the recommended ProHance dose and allow a sufficient period of time for
elimination of the drug prior to re-administration. For patients receiving
hemodialysis, physicians may consider the prompt initiation of hemodialysis
following the administration of a GBCA in order to enhance the contrast agent's
elimination. The usefulness of hemodialysis in the prevention of NSF is unknown
(see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Deoxygenated sickle erythrocytes have been shown in in vitro
studies to align perpendicular to a magnetic field which may result in
vaso-occlusive complications in vivo. The enhancement of magnetic moment by
ProHance may possibly potentiate sickle erythrocyte alignment. ProHance in
patients with sickle cell anemia and other hemoglobinopathies has not been
studied.

Patients with other hemolytic anemias have not been
adequately evaluated following administration of ProHance to exclude the
possibility of increased hemolysis.

Patients with a history of allergy, drug reactions or other
hypersensitivity-like disorders should be closely observed during the procedure
and for several hours after drug administration. (See PRECAUTIONS-General).

PRECAUTIONS

General

Gadoteridol is cleared from the body by glomerular
filtration. The hepato-biliary enteric pathway of excretion has not been
demonstrated with ProHance®. Dose adjustments in renal or hepatic impairment
have not been studied. Therefore, caution should be exercised in patients with
either renal or hepatic impairment.

In a patient with a history of grand mal seizure, the possibility
to induce such a seizure by ProHance® is unknown.

The possibility of a reaction, including serious, life
threatening, or fatal, anaphylactic or cardiovascular reactions, or other
idiosyncratic reactions (see ADVERSE REACTIONS), should always be considered,
especially in those patients with a history of a known clinical hypersensitivity
or a history of asthma or other allergic respiratory disorders.

Diagnostic procedures that involve the use of contrast
agents should be carried out under direction of a physician with the
prerequisite training and a thorough knowledge of the procedure to be
performed.

When ProHance (Gadoteridol) Injection is to be injected
using nondisposable equipment, scrupulous care should be taken to prevent
residual contamination with traces of cleansing agents. After ProHance is drawn
into a syringe, the solution should be used immediately.

Carcinogenesis, Mutagenesis, And Impairment Of Fertility

No animal studies have been performed to evaluate the
carcinogenic potential of gadoteridol or potential effects on fertility.

ProHance did not demonstrate genotoxic activity in bacterial
reverse mutation assays using Salmonella typhimurium and Escherichia coli, in a
mouse lymphoma forward mutation assay, in an in vitro cytogenetic assay
measuring chromosomal aberration frequencies in Chinese hamster ovary cells,
nor in an in vivo mouse micronucleus assay at intravenous doses up to 5.0
mmol/kg.

Pregnancy Category C

ProHance administered to rats at 10 mmol/kg/day (33 times
the maximum recommended human dose of 0.3 mmol/kg or 6 times the human dose
based on a mmol/m² comparison) for 12 days during gestation doubled the
incidence of postimplantation loss. When rats were administered 6.0 or 10.0
mmol/kg/day for 12 days, an increase in spontaneous locomotor activity was
observed in the offspring. ProHance increased the incidence of spontaneous
abortion and early delivery in rabbits administered 6 mmol/kg/day (20 times the
maximum recommended human dose or 7 times the human dose based on a mmol/m² comparison)
for 13 days during gestation.

There are no adequate and well-controlled studies in
pregnant women. ProHance (Gadoteridol) Injection should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
ProHance is administered to a nursing woman.

Pediatric Use

Safety and efficacy in children under the age of 2 years
have not been established. The safety and efficacy of doses > 0.1 mmol/kg;
and sequential and/or repeat procedures has not been studied in children. (See INDICATIONS
AND USAGE and DOSAGE AND ADMINISTRATION sections)

Last reviewed on RxList: 7/13/2012
This monograph has been modified to include the generic and brand name in many instances.